The Gulf Long-term Follow-up Study (GuLF STUDY, www.gulfstudy.nih.gov) was initiated in response to the April 2010 explosion of the Deepwater Horizon (DWH) drilling rig and resulting oil spill in the Gulf of Mexico, the largest marine oil spill in U.S. history. Building on telephone and in-person data collection efforts that began in 2011, NIEHS has amassed an a large amount data on 32,608 individuals who completed a telephone enrollment questionnaire between 2011-2013 and continue to be followed. Over 11,000 participants from Gulf states completed a home visit to provide additional questionnaire as well as anthropometric, physiologic, and biospecimen data (n=11,193). These data are being used to explore a variety of different outcomes stemming including respiratory, cardiovascular, dermatologic, mental health, neurological, hepatic, renal, endocrine, hematological, and other systemic effects. Follow-up data were collected on 21,256 participants between 2013-2016. With financial support from SAMHSA, additional information was collected on mental health trajectories for a subset of 2,859 individuals between 2013-2016. Of these individuals, 1,506 completed all 4 repeated data collection opportunities. A subset of 3,403 participants completed a more comprehensive clinical exam (2014-2016). that included additional measures of lung function, standardized measures of neurological function, questionnaires, and biological sample collection. All participants, regardless of active participation in follow up interviews or exam, are followed over time via linkage to cancer and mortality records. The first cohort-wide (except for Vietnamese-speaking participants) follow-up interview was completed in May 2016. The interview assessed changes in health status and factors that could confound associations between exposures and outcomes. A second follow-up interview cycle began in 2018. In addition to updating previously collected questionnaire data, the new interview adds questions about fertility and reproductive health. There are also new questions on sleep, metabolic health, and social factors to enable studies of health disparities. As part of this interview, we validate self-reported health endpoints through questions on medications or treatments that support the diagnosis (e.g. use of insulin or oral agents by diabetics), and request medical record release authorization for selected conditions. A unique aspect of this work is the extensive characterization of oil spill exposures. We used questionnaires and measurement data to develop an ordinal job-exposure matrix (JEM) for airborne THC as a composite marker for oil spill exposures. We also developed ordinal measures for exposure to dispersants and particulates from burning oil using questionnaires and external information we gathered about OSRC activities and requirements. We used questionnaire data to identify groups of jobs/tasks with likely similar exposures and used the measurement data from monitoring that took place during the clean-up to characterize the exposures in those jobs. Exposures were found to vary by location, task, and time in relation to the capping of the well, among other factors. Methods were developed and/or evaluated to identify the least biased way to deal with values below the LOD and other censoring. New quantitative measures have recently been developed. These measures incorporate time spent in various jobs/tasks and additional information from measurements made during the spill and industry and government documentation of cleanup activities. Ongoing analysis of baseline and follow-up data continues to be focused on mental health, pulmonary function, cardiovascular outcomes, respiratory health, neurologic symptoms, and a range of specific and non-specific symptoms reported by participants while working on the response and clean-up. A recent analysis showed that mental health symptoms were increased with increasing number of disaster experiences, with greater levels of depression and PTSD-like symptoms among persons who experienced both disruption due to Hurricane Katrina and worked on oil spill clean-up (Lowe et al. 2019). Pulmonary function testing was done during the GuLF STUDY home exams. Workers who handled oily wildlife (plants, birds, dead animal) had significantly reduced lung function (Gam et al., 2018) compared to a nationally representative sample. A current analysis is considering changes in lung function over time since the clean-up. Several analyses considered risk of MI in relation to various oil spill exposures. Risk for incident nonfatal MI was suggestively increased among those who cleaned up after the oil spill (Strelitz et al., 2018). Total MI fatal and nonfatal MI over 5 years of follow-up was also shown to be associated with higher levels of exposure to hydrocarbons (Strelitz et al. 2019). Ongoing and future work will evaluate associations with chemical-specific quantitative exposure measures and consider changes in symptoms and clinical measures over time Details of the development of an ordinal exposure measurement algorithm were published (Stewart et al., 2018). Other measures were recently completed included quantitative, time-dependent metrics for total hydrocarbons and specific oil spill chemicals, PM2.5 from burning. Methods to characterize dermal exposure was also published (Gorman et al. 2019). Although not an oil spill chemical, per se, blood levels of styrene had been found to be higher among Gulf coast residents participating in this study compared to levels from a U.S. population sample (NHANES). Styrene, at occupational exposure levels, is a neurotoxin. We investigated the potential link between population level styrene exposures and neurological symptoms and function. Two exposure measures were used blood levels of styrene, and ambient exposures as estimated using an EPA national air toxics database linked to the residences of GuLF STUDY participants. Styrene was suggestively associated with both symptoms and several specific tests of neurological function (Werder et al., 2018; Werder et al. 2019). Other recent papers from the study describe predictors of current levels of blood volatile organic compounds (Werder et al. 2018), and symptoms associated with potential exposure to dispersants, and changes in hematologic measures associated with BTEX exposures. Ongoing and future work will evaluate associations with chemical-specific quantitative exposure measures and consider changes in symptoms and clinical measures over time. Analysis of biospecimens is underway with measurements of kidney and liver bioassays in relation to chemical exposures. An epigenome wide study of methylation in blood and a genome-wide association study are being carried out in a sample of participants selected based on total hydrocarbon and burning exposure levels as well specific health outcomes, for studies of epigenetic effects of chemical exposures and the influence of epigenetic and genetic factors on specific health outcomes such as pulmonary function.